Stearic acid, monoester with propane-1,2-diol

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

other: weight of evidence analysis based on expert evaluated data on hydrolysis products and structural analogues

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: based on expert group reviews

Justification for type of information:

Stearic acid, monoester with propane-1,2-diol (PGMS) is manufactured by a reaction between stearic acid and propylene glycol. PGMS is a UVCB substance belonging to the group of fatty acid esters. The two main constituents of the UVCB substance are the monoester of propane-diol with octadecanoic acid (45-98%) and the monoester of propane-diol with palmitic acid (2-50%).

Within this group is the group of polyglycerol fatty acid esters, which are commonly used in cosmetics and as food ingredients representing substances composed of chemical units of similar structure as the fatty acid esters with propylene glycol. The polyglycerol fatty acids are esters of fatty acids and units of glycerol. The glycerol units represent the propylene glycol in “Stearic acid, monoester with propane-1,2-diol”.
To assess the reproductive/developmental toxicity of the substance, the toxicity of fatty acid (stearic acids) in general is therefore considered. As supplementary data, also studies reviewed on propane-1,2-diol is included.

A weight of evidence document is attached. The conclusion in this document is based on data from the following expert assessments:

CIR (2019). Safety Assessment of Fatty Acids & Fatty Acid Salts as Used in Cosmetics, Tentative Report for Public Commenting, January 4, 2019
EFSA (2018a). Re-evaluation of propane-1,2-diol esters of fatty acids (E 477) as a food additive EFSA Panel on Food Additives and Flavourings (FAF). EFSA Journal 2018;16(12):5497
EFSA (2018b). Re-evaluation of propane-1,2-diol (E 1520) as a food additive EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2018;16(4):5235

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Principles of method if other than guideline:

In relation to the data requirements of REACH Annex VIII (10-100 t/y), data on screening for reproductive/developmental toxicity must be provided. Data on this endpoint are not available for Stearic acid, monoester with propane-1,2-diol (PGMS). The possible reproductive/developmental toxicity of the UVCB substance is therefore assessed in the present weight of evidence analysis based on existing data on the relevant hydrolysis products and the components in the UVCB substance.

Metabolism studies of propane-1,2-diol esters of stearate show that the substances are partially hydrolysed by pancreatic lipase; approx. 70% in 15 h. As the passage through the small intestine has a duration of 6–8 h, unhydrolyzed propane-1,2-diol esters of stearate will be present in the gastrointestinal tract for absorption (EFSA 2018a). However, as no data is available for propane-1,2-diol esters of fatty acids, i.e. PGMS (EFSA 2018a), the present analysis will be based on the relevant hydrolysis products propane-1,2-diol (EFSA 2018b) and fatty acids (CIR 2019).

As the substance is an UVCB-substance and as expert group assessments of the components in the substances are considered the most valid data for the assessment, an overall weight of evidence approach is used for the assessment.

Test material

Test material information

1

Reference substance name:

Stearic acid, monoester with propane-1,2-diol

EC Number:

215-354-3

EC Name:

Stearic acid, monoester with propane-1,2-diol

Cas Number:

1323-39-3

Molecular formula:

C21H42O3

IUPAC Name:

2-hydroxypropyl stearate

Test material form:

solid: pellets

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Key result

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day (nominal)

Sex:

not specified

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity (P0)

Critical effects observed:

no

Results: F1 generation

Effect levels (F1)

Key result

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day (nominal)

Sex:

not specified

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity (F1)

Critical effects observed:

no

Overall reproductive toxicity

Key result

Reproductive effects observed:

no

Any other information on results incl. tables

No studies in relation to reproductive toxicity are available for Stearic acid, monoester with propane-1,2-diol (PGMS). Data were therefore obtained for fatty acids (stearates) and the relevant hydrolysis products and the
components in the UVCB substance (propane-1,2-diol). 

In the evaluation of the safety of use in cosmetic products, dermal and oral studies of several fatty acid and fatty acid salts in relation to reproductive/developmental toxicity were summarized. In general, no treatment
related reproductive or developmental effects were seen in the studies (CIR 2019).

A dermal study in accordance with OECD TG 422 was performed on Lithium Stearate with doses of 0, 100, 300, or 1000 mg/kg/ day in Sprague-Dawley rats (10 sex per dose group). No treatment-related adverse reproductive effects in parental animals and no treatment-related adverse effects in development of
offspring. A NOAEL > 1000 mg/kg bw/day was set. Further, an oral study (oral gavage) was performed with calcium stearate also in Sprague-Dawley rats receiving 0, 250, 500, or 1000 mg/kg bw/day in corn oil. Similarly, a NOAEL = 1000 mg/kg bw/day for parental animals and for offspring was found; no treatment-related adverse effects were observed (CIR 2019).

In the evaluation of propane-1,2-diol as a food additive, the reproductive and developmental toxicity was addressed in several studies (EFSA 2018b). Overall, the EFSA panel concluded that there are no adverse effects on reproductive toxicity parameters of propane-1,2-diol up to 10,118 mg propane-1,2-diol/kg bw per day in drinking water in a continuous breeding reproduction study in mice or in a fertility study in male and female rats given propane-1,2-diol (1000 mg/kg bw per day) daily by gavage. No adverse maternal or
developmental effects were observed in prenatal developmental toxicity studies with mice, rats, hamsters, and rabbits given propane-1,2-diol by oral gavage at dose levels up to 1600, 1600, 1550 and 1230 mg/kg bw per day, respectively, on GD 6–15, 6–15, 6–10 and 6–18, respectively (EFSA 2018b).

Based on the studies available for the stearate fatty acids and propane-1,2-diol, it can with a high degree of confidence be concluded no adverse effects on fertility and developmental endpoints would be expected and that an assumed NOAEL for PGMS will be > 1000 mg/kg bw/day which is normally considered as the highest relevant dose level when testing for reproduction and prenatal developmental toxicity. Thus, PGMS is not to be classified for reproductive or developmental toxicity.

Overall, the available information comprises adequate, reliable studies from reference substances with similar structure and intrinsic properties. Weight-of-evidence is justified based on common functional group and common precursors/breakdown products. The information from these independent sources is consistent and provides sufficient weight of evidence leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006.

Applicant's summary and conclusion

Conclusions:

No studies in relation to reproductive toxicity are available for Stearic acid, monoester with propane-1,2-diol (PGMS). The possible reproductive toxicity of the UVCB substance is therefore assessed in the present weight of evidence analysis based on existing data on the relevant hydrolysis products and the components in the UVCB substance. Based on the studies available for the stearate fatty acids and propane-1,2-diol, it can with a high degree of confidence be concluded that no adverse effects on fertility and developmental endpoints would be expected and that an assumed NOAEL for Stearic acid, monoester with propane-1,2-diol (PGMS) will be > 1000 mg/kg bw/day which is normally considered as the highest relevant dose level when testing for reproduction and prenatal developmental toxicity. Thus, PGMS is not to be classified for reproductive or developmental toxicity.

Overall, the available information comprises adequate, reliable studies from
reference substances with similar structure and intrinsic properties. Weight-ofevidence is justified based on common functional group and common
precursors/breakdown products. The information from these independent
sources is consistent and provides sufficient weight of evidence leading to an
endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No
1907/2006.

Executive summary:

No studies in relation to reproductive toxicity are available for Stearic acid, monoester with propane-1,2-diol (PGMS). The possible reproductive toxicity of the UVCB substance is therefore assessed in the present weight of evidence analysis based on existing data on the relevant hydrolysis products and the components in the UVCB substance.

 

Metabolism studies of propane-1,2-diol esters of stearate show that the substances are partially hydrolysed by pancreatic lipase; approx. 70% in 15 h. As the passage through the small intestine has a duration of 6–8 h, unhydrolyzed propane-1,2-diol esters of stearate will be present in the gastrointestinal tract for absorption (EFSA 2018a). However, as no data is available for propane-1,2-diol esters of fatty acids, i.e. PGMS (EFSA 2018a), the present analysis is based on the relevant hydrolysis products propane-1,2-diol (EFSA 2018b) and fatty acids (CIR 2019).

 

In the evaluation of the safety of use in cosmetic products, dermal and oral studies of several fatty acid and fatty acid salts in relation to reproductive/developmental toxicity were summarized. In general, no treatment related reproductive or developmental effects were seen in the studies (CIR 2019).

 

A dermal study in accordance with OECD TG 422 was performed on Lithium Stearate with doses of 0, 100, 300, or 1000 mg/kg/ day in Sprague-Dawley rats (10 sex per dose group). No treatment-related adverse reproductive effects in parental animals and no treatment-related adverse effects in development of offspring. A NOAEL > 1000 mg/kg bw/day was set. Further, an oral study (oral gavage) was performed with calcium stearate also in Sprague-Dawley rats receiving 0, 250, 500, or 1000 mg/kg bw/day in corn oil. Similarly, a NOAEL = 1000 mg/kg bw/day for parental animals and for offspring was found; no treatment-related adverse effects were observed (CIR 2019).

 

In the evaluation of propane-1,2-diol as a food additive, the reproductive and developmental toxicity was addressed in several studies (EFSA 2018b). Overall, the EFSA panel concluded that there are no adverse effects on reproductive toxicity parameters of propane-1,2-diol up to 10,118 mg propane-1,2-diol/kg bw per day in drinking water in a continuous breeding reproduction study in mice or in a fertility study in male and female rats given propane-1,2-diol (1000 mg/kg bw per day) daily by gavage. No adverse maternal or developmental effects were observed in prenatal developmental toxicity studies with mice, rats, hamsters and rabbits given propane-1,2-diol by oral gavage at dose levels up to 1600, 1600, 1550 and 1230 mg/kg bw per day, respectively, on GD 6–15, 6–15, 6–10 and 6–18, respectively (EFSA 2018b).

 

Based on the studies available for the stearate fatty acids and propane-1,2-diol, it can be concluded that no adverse effects on fertility and developmental endpoints would be expected and that an assumed NOAEL for PGMS will be > 1000 mg/kg bw/day which is normally considered as the highest relevant dose level when testing for reproduction and prenatal developmental toxicity. Thus, PGMS is not to be classified for reproductive or developmental toxicity.

 

Overall, the available information comprises adequate, reliable studies from reference substances with similar structure and intrinsic properties. Weight-of - evidence is justified based on common functional group and common precursors/breakdown products. The information from these independent sources is consistent and provides sufficient weight of evidence leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006.